567 research outputs found

    Early liver biopsy, intraparenchymal cholestasis, and prognosis in patients with alcoholic steatohepatitis

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    <p>Abstract</p> <p>Background</p> <p>Alcoholic steatohepatitis (ASH) is a serious complication of alcoholic liver disease. The diagnosis of ASH requires the association of steatosis, evidence of hepatocellular injury with ballooning degeneration, and polynuclear neutrophil infiltration on liver biopsy. Whether these lesions, in addition to other histological features observed in liver tissue specimens, have prognostic significance is unclear.</p> <p>Methods</p> <p>We studied 163 patients (age 55 yrs [35-78], male/female 102/61) with recent, heavy (> 80 gr/day) alcohol intake, histologically-proven ASH (97% with underlying cirrhosis, Maddrey's score 39 [13-200], no sepsis), who had a liver biopsy performed 3 days [0-10] after hospital admission for clinical decompensation. A semi-quantitative evaluation of steatosis, hepatocellular damage, neutrophilic infiltration, periportal ductular reaction, intraparenchymal cholestasis, and iron deposits was performed by two pathologists. All patients with a Maddrey's score ≥ 32 received steroids. The outcome at 3 months was determined. Statistical analysis was performed using the Wilcoxon and Fisher's exact tests, Kaplan-Meier method, and the Cox proportional hazard model.</p> <p>Results</p> <p>43 patients died after 31 days [5-85] following biopsy. The 3-month survival rate was 74%. Mean kappa value for histological assessment by the two pathologists was excellent (0.92). Univariate analysis identified age, the Maddrey's score, the Pugh's score, the MELD score and parenchymal cholestasis, but not other histological features, as factors associated with 3-month mortality. At multivariate analysis, age (p = 0.029, OR 2.83 [1.11-7.2], intraparenchymal cholestasis (p = 0.001, OR 3.9 [1.96-7.8], and the Maddrey's score (p = 0.027, OR 3.93 [1.17-13.23] were independent predictors of outcome. Intraparenchymal cholestasis was more frequent in non survivors compared to survivors (70% versus 25%, p < 0.001). Serum bilirubin was higher in patients with severe compared to those with no or mild intraparenchymal cholestasis (238 [27-636] versus 69 [22-640] umol/l, p < 0.001).</p> <p>Conclusions</p> <p>In this large cohort of patients with histologically documented ASH early after admission and no sepsis, liver biopsy identified marked intraparenchymal cholestasis as an independent predictor of poor short term outcome together with age and the Maddrey's score. It may be hypothesized that incorporation of this particular variable into existing disease severity scores for ASH would improve their performance.</p

    Post Eruption inflation of the East Pacific Rise at 9°50′ N

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    In June 2008, we installed a geodetic network at 9°50′ N on the East Pacific Rise to track the long‐term movement of magma following the 2005/6 eruption. This network consists of 10 concrete benchmarks stretching from the ridge to 9 km off‐axis. During three campaign‐style surveys, measurements of vertical seafloor motions were made at each of these benchmarks by precisely recording ambient seawater pressure as a proxy for seafloor depth with a mobile pressure recorder (MPR). The MPR was deployed using the manned submersible Alvin in 2008 and 2009 and the remotely operated vehicle Jason in 2011. The MPR observations are supplemented with data from a multiyear deployment of continuously recording bottom pressure recorders (BPRs) extending along this segment of the ridge that can record rapid changes in seafloor depth from seafloor eruptions and/or dike intrusions. These measurements show no diking events and up to 12 cm of volcanic inflation that occurred from December 2009 to October 2011 in the area of the 2005/6 eruption. These observations are fit with an inflating point source at a depth of 2.7 km and volume change of 2.3 × 106 m3/yr located on the ridge axis at approximately 9°51.166′ N, 407 m from our northernmost benchmark, suggesting that the magma chamber underlying this segment of the ridge is being recharged from a deeper source at a rate that is about half the long‐term inflation rate observed at Axial Seamount on the Juan de Fuca Ridge. These data represent the second location that active volcanic uplift has been measured on a mid‐ocean ridge segment, and the first on a nonhotspot influenced segment

    Lack of in vivo blockade of Fas- and TNFR1-mediated hepatocyte apoptosis by the hepatitis C virus.

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    In vitro data have shown that the hepatitis C virus (HCV) core protein binds to protein members of the tumour necrosis factor receptor (TNFR) superfamily. Since this interaction could be relevant to HCV persistence and oncogenesis, this study assessed whether HCV may interfere with the apoptotic cascade in vivo. Apoptosis (by TUNEL) and Fas and TNFR1 expression (by immunohistochemistry) were scored in the liver of 60 chronic hepatitis C patients. Results were compared with the liver disease grading and staging scores and the HCV replication level in serum and liver. Apoptotic hepatocytes were stained in 29 cases. Fas was expressed in 35 cases and TNFR1 in 21, 15 patients (25%) being negative for both receptors. Overall, the numbers of TUNEL-, Fas- and TNFR-positive hepatocytes did not correlate with the extent of intrahepatic CD8+ T-lymphocyte infiltration, the grading and staging of liver disease, or the serum or liver HCV RNA levels. Furthermore, when patients expressing either Fas or TNFR1 were stratified according to serum HCV RNA levels, cases with detectable hepatocyte apoptosis had higher HCV viraemias. In conclusion, an HCV-mediated, in vivo blockade of hepatocyte apoptosis via the Fas- or TNFR1-dependent pathways seems unlikely

    Survey Simulations of a New Near-Earth Asteroid Detection System

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    We have carried out simulations to predict the performance of a new space-based telescopic survey operating at thermal infrared wavelengths that seeks to discover and characterize a large fraction of the potentially hazardous near-Earth asteroid (NEA) population. Two potential architectures for the survey were considered: one located at the Earth-Sun L1 Lagrange point, and one in a Venus-trailing orbit. A sample cadence was formulated and tested, allowing for the self-follow-up necessary for objects discovered in the daytime sky on Earth. Synthetic populations of NEAs with sizes >=140 m in effective spherical diameter were simulated using recent determinations of their physical and orbital properties. Estimates of the instrumental sensitivity, integration times, and slew speeds were included for both architectures assuming the properties of new large-format 10 um detector arrays capable of operating at ~35 K. Our simulation included the creation of a preliminary version of a moving object processing pipeline suitable for operating on the trial cadence. We tested this pipeline on a simulated sky populated with astrophysical sources such as stars and galaxies extrapolated from Spitzer and WISE data, the catalog of known minor planets (including Main Belt asteroids, comets, Jovian Trojans, etc.), and the synthetic NEA model. Trial orbits were computed for simulated position-time pairs extracted from the synthetic surveys to verify that the tested cadence would result in orbits suitable for recovering objects at a later time. Our results indicate that the Earth-Sun L1 and Venus-trailing surveys achieve similar levels of integral completeness for potentially hazardous asteroids larger than 140 m; placing the telescope in an interior orbit does not yield an improvement in discovery rates. This work serves as a necessary first step for the detailed planning of a next-generation NEA survey.Comment: AJ accepted; corrected typ

    Proteomic analysis of interchromatin granule clusters

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    A variety of proteins involved in gene expression have been localized within mammalian cell nuclei in a speckled distribution that predominantly corresponds to interchromatin granule clusters (IGCs). We have applied a mass spectrometry strategy to identify the protein composition of this nuclear organelle purified from mouse liver nuclei. Using this approach, we have identified 146 proteins, many of which had already been shown to be localized to IGCs, or their functions are common to other already identified IGC proteins. In addition, we identified 32 proteins for which only sequence information is available and thus these represent novel IGC protein candidates. We find that 54% of the identified IGC proteins have known functions in pre-mRNA splicing. In combination with proteins involved in other steps of pre-mRNA processing, 81% of the identified IGC proteins are associated with RNA metabolism. In addition, proteins involved in transcription, as well as several other cellular functions, have been identified in the IGC fraction. However, the predominance of pre-mRNA processing factors supports the proposed role of IGCs as assembly, modification, and/or storage sites for proteins involved in pre-mRNA processing

    ExploreNEOs I: Description and first results from the Warm Spitzer NEO Survey

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    We have begun the ExploreNEOs project in which we observe some 700 Near Earth Objects (NEOs) at 3.6 and 4.5 microns with the Spitzer Space Telescope in its Warm Spitzer mode. From these measurements and catalog optical photometry we derive albedos and diameters of the observed targets. The overall goal of our ExploreNEOs program is to study the history of near-Earth space by deriving the physical properties of a large number of NEOs. In this paper we describe both the scientific and technical construction of our ExploreNEOs program. We present our observational, photometric, and thermal modeling techniques. We present results from the first 101 targets observed in this program. We find that the distribution of albedos in this first sample is quite broad, probably indicating a wide range of compositions within the NEO population. Many objects smaller than one kilometer have high albedos (>0.35), but few objects larger than one kilometer have high albedos. This result is consistent with the idea that these larger objects are collisionally older, and therefore possess surfaces that are more space weathered and therefore darker, or are not subject to other surface rejuvenating events as frequently as smaller NEOs.Comment: AJ in pres

    ExploreNEOs. II. The Accuracy of the Warm Spitzer Near-Earth Object Survey

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    We report on results of observations of near-Earth objects (NEOs) performed with the NASA Spitzer Space Telescope as part of our ongoing (2009-2011) Warm Spitzer NEO survey ("ExploreNEOs"), the primary aim of which is to provide sizes and albedos of some 700 NEOs. The emphasis of the work described here is an assessment of the overall accuracy of our survey results, which are based on a semi-empirical generalized model of asteroid thermal emission. The NASA Spitzer Space Telescope has been operated in the so-called Warm Spitzer mission phase since the cryogen was depleted in 2009 May, with the two shortest-wavelength channels, centered at 3.6 μm and 4.5 μm, of the Infrared Array Camera continuing to provide valuable data. The set of some 170 NEOs in our current Warm Spitzer results catalog contains 28 for which published taxonomic classifications are available, and 14 for which relatively reliable published diameters and albedos are available. A comparison of the Warm Spitzer results with previously published results ("ground truth"), complemented by a Monte Carlo error analysis, indicates that the rms Warm Spitzer diameter and albedo errors are ±20% and ±50%, respectively. Cases in which agreement with results from the literature is worse than expected are highlighted and discussed; these include the potential spacecraft target 138911 2001 AE_2. We confirm that 1.4 appears to be an appropriate overall default value for the relative reflectance between the V band and the Warm Spitzer wavelengths, for use in correction of the Warm Spitzer fluxes for reflected solar radiation

    Observational Constraints on the Catastrophic Disruption Rate of Small Main Belt Asteroids

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    We have calculated 90% confidence limits on the steady-state rate of catastrophic disruptions of main belt asteroids in terms of the absolute magnitude at which one catastrophic disruption occurs per year (HCL) as a function of the post-disruption increase in brightness (delta m) and subsequent brightness decay rate (tau). The confidence limits were calculated using the brightest unknown main belt asteroid (V = 18.5) detected with the Pan-STARRS1 (Pan-STARRS1) telescope. We measured the Pan-STARRS1's catastrophic disruption detection efficiency over a 453-day interval using the Pan-STARRS moving object processing system (MOPS) and a simple model for the catastrophic disruption event's photometric behavior in a small aperture centered on the catastrophic disruption event. Our simplistic catastrophic disruption model suggests that delta m = 20 mag and 0.01 mag d-1 < tau < 0.1 mag d-1 which would imply that H0 = 28 -- strongly inconsistent with H0,B2005 = 23.26 +/- 0.02 predicted by Bottke et al. (2005) using purely collisional models. We postulate that the solution to the discrepancy is that > 99% of main belt catastrophic disruptions in the size range to which this study was sensitive (100 m) are not impact-generated, but are instead due to fainter rotational breakups, of which the recent discoveries of disrupted asteroids P/2013 P5 and P/2013 R3 are probable examples. We estimate that current and upcoming asteroid surveys may discover up to 10 catastrophic disruptions/year brighter than V = 18.5.Comment: 61 Pages, 10 Figures, 3 Table
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